Microfluidic systems have advanced to the point where they are beginning to supplant conventional technologies in biological, chemical and biochemical analyses. For example, routine separation based analyses, e.g., nucleic acid separations, protein sizing separations, and the like are now routinely performed in microfluidic systems, e.g., the Agilent 2100 Bioanalyzer and Caliper LabChip® systems. Similarly, high throughput analytical operations, e.g., pharmaceutical screening, high throughput genetic analysis, and the like, are also being transitioned from multi-well formats into microfluidic formats, such as the Caliper HTS sipper chip systems. These microfluidic systems have allowed for increases in throughput while requiring substantially smaller volumes of reagents, smaller equipment footprint, and having more reproducible, automatable, integratable operations.
As with any advancing technology however, the miniaturization of analytical chemistries introduces a number of additional considerations. For example, in conventional scale chemical or biochemical analyses, problems associated with interaction between reagents and reaction vessels are kept to a minimum by virtue of the overwhelming volume of reagents used. Similarly, the nature of the reaction vessels used in conventional technologies, while illustrating the advantages of microfluidic systems, also obviate some of the potential problems of microfluidic systems. For example, because these reaction vessels are typically configured as discrete wells or test tubes, there is little or no issue of interaction between discrete reactions that are being analyzed. Similarly, the open-top nature of these vessels allows the evolution of other interfering components, which is not reasonably practicable in sealed microfluidic channels.
In enclosed microfluidic systems, however, the channel surface to volume ratio is substantially increased over conventional technologies, increasing the effects that those surfaces have on the contents of those channels. Further, because of their enclosed nature, one cannot readily access and control the reactions as they progress through the system. In addition, the sealed nature of these systems can result in the accumulation of evolved gasses from the fluid reagents of a system, where such gases would dissipate into the atmosphere in conventional assay formats.
A number of stop-gap measures have been employed in attempts to address some of these potential problems of microfluidic systems. For example, U.S. Pat. No. 5,880,071 describes methods of reducing effects of electrokinetic biasing of reagents within electrically driven microfluidic channel systems. Similarly, U.S. Pat. No. 6,043,080 to Lipshutz et al., describes the use of gas venting membranes within a miniature chamber, to permit degassing of fluids within a miniature fluidic environment.